Proper coordination of cholesterol biosynthesis and trafficking is essential to human health. The sterol regulatory element binding proteins (SREBPs) are key transcription regulators of genes involved in cholesterol biosynthesis/uptake. We show here that microRNAs (miR-33a/b) embedded within introns of the SREBP genes target the ATP-binding cassette transporter A1 (ABCA1), an important regulator of high-density lipoprotein (HDL) synthesis and reverse cholesterol transport, for post-transcriptional repression. Antisense inhibition of miR-33 in cell lines causes upregulation of ABCA1 expression and increased cholesterol efflux, and injection of mice on a western-type diet with locked nucleic acid (LNA)-antisense oligonucleotides results in elevated plasma HDL. Collectively, our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis, and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases.

Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet–fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders.

CuCl-based ionic liquid was synthesized by mixing 1-butyl-3-methylimidazolium chloride with purified anhydrous CuCl, and its structures were studied using fast atom bombardment mass spectrometry (FAB-MS). It was determined that Cu(I) anionic species such as CuCl 2 -, Cu 2 Cl 3 -, and Cu 3 Cl 4existed in the ionic liquid, and these anions were moisture-insensitive and stable in air. CuCl-based ionic liquid exhibited remarkable desulfurization ability in the desulfurization of gasoline when used as an extraction absorbent. The effectiveness of sulfur removal may be attributed to the π-complexation of Cu(I) with thiophene, which shows promise as an approach for the deep desulfurization of motor fuel.